title: Effect of blonanserin on methamphetamine-induced disruption of latent inhibition and c-Fos expression in rats.
abstract: To clarify the psychopharmacological profile of blonanserin, a novel antipsychotic, we examined its effect on the methamphetamine-induced disruption of latent inhibition (LI) and the neural activation related to this effect in rats. To evaluate the LI, we used a conditioned emotional response in which a tone (conditioned stimulus) was paired with a mild foot shock (unconditioned stimulus). This paradigm was presented to rats licking water. Methamphetamine-induced (1.0mg/kg, i.p.) disruption of LI was significantly improved by the administration of a higher dose (3.0mg/kg, i.p.) of blonanserin and tended to be improved by 1.0-mg/kg blonanserin and 0.2-mg/kg haloperidol but not by a lower dose (0.3mg/kg) of blonanserin. Immunohistochemical examination showed blonanserin (3.0mg/kg, i.p.) increased c-Fos expression in the shell area but not in the core area of the nucleus accumbens while methamphetamine (3.0mg/kg, i.p.) produced the opposite expression pattern. Blonanserin also increased the number of c-Fos expressions in the central amygdala nucleus but not in the basolateral amygdala nucleus or the prefrontal cortex. Blonanserin ameliorates the methamphetamine-induced disruption of LI, as other antipsychotics do, and a neuronal activation and/or modulation of neurotransmission in the nucleus accumbens is related to the disruption of LI by methamphetamine and to its amelioration by blonanserin.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-city, Miyazaki 889-1692, Japan. m11072@fc.miyazaki-u.ac.jp
authors.forename: Aki
authors.initials: A
authors.lastname: Kuramashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
authors.forename: Go
authors.initials: G
authors.lastname: Koganemaru
authors.forename: Hisae
authors.initials: H
authors.lastname: Matsuo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ebihara
authors.forename: Hideki
authors.initials: H
authors.lastname: Funahashi
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Takeda
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nishimori
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishida
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D008694:Methamphetamine; C079310:blonanserin
keywords: Blonanserin; Haloperidol; Immediate-early gene protein; Latent inhibition; Schizophrenia